This project is the central core of a broad program wich is directed towards the investigaton of a variety of fundamental, immunological problems associated with the Connective Tissue Diseases, particularly Systemic Lupus Erythematosus. For the past 10 years, this project grant has been instrumental in supporting and developing specific research activities of the Rheumatology Division which relate to the interface between humoral and cellular immunology. This renewal grant continues to focus on: (1) The demonstration, isolation, and analysis of immune complexes using several methods which appear to define complexes based on different properties; (2) receptors on subpopulations of lymphocytes which may interact with these complexes; (3) the effects of immune complex-cellular interactions with special attention now to (a) a third population - "non-B, non-T" or "L lymphocyte" which has an avid receptor for IgG, (b) subpopulations of T-cells which have receptors that are either specific for IgG or IgM, and (c) serum factors such as complement, rheumatoid factors and immunoconglutinin which may modulate the immune complex-cellular interaction; (4) mediators released by lymphocytes after interaction with immune complexes, and (5) a new direction which is the study of immune complexes in two recently discovered examples of murine lupus. It is hoped that by further understanding of these humoral-cellular interactions, more rational therapy for some of the rheumatic diseases will be forthcoming.